Distal phalangeal erythema in an infant with biallelic PDSS1 mutations: Expanding the phenotype of primary Coenzyme Q10 deficiency.

We report a detailed clinical examination in a patient with primary coenzyme Q10 deficiency caused by biallelic mutations in the PDSS1 gene who presented clinical features of mitochondrial encephalopathy associated with pulmonary hypertension, livedo reticularis and particularly, chronic distal phalangeal erythema. Laboratory testing showed elevated plasma lactate and 3-methyl-glutaconic and tricarboxylic aciduria. Supplementation with high dose of coenzyme Q10 was not effective to control disease progression and the patient died at the age of 3 years old because of a progressive multisystem disorder. Cutaneous involvement in mitochondrial disease is heterogenous, including proliferative, inflammatory, and dystrophic changes among others. The coexistence in our case of phalangeal erythema, livedo reticularis, and pulmonary hypertension suggests microvascular dysfunction as a possible underlying mechanism. This is the first reported patient with PDSS1 mutations presenting with 3-methyl-glutaconic aciduria and distal phalangeal erythema, expanding the phenotype of primary coenzyme Q10 deficiency.

Activation and deactivation patterns in schizophrenia during performance of an fMRI adapted version of the stroop task.

The Stroop task, which examines an aspect of executive function/cognitive control, the ability to inhibit prepotent responses, has been relatively little examined in schizophrenia, and the findings have been inconsistent. Whether performance of this task is associated with failure of de-activation in the disorder is also uncertain. We examined 42 schizophrenic patients and 61 healthy controls during performance of an fMRI-adapted version of the Stroop task, the counting Stroop task. Task-related activations (incongruent > congruent condition) and de-activations (baseline > incongruent) were examined using whole-brain, voxel-based methods. In the healthy controls, task performance was found to be associated with activations in the left dorsolateral prefrontal cortex and the dorsal anterior cingulate cortex, among other regions. De-activations were seen in the medial frontal cortex, the middle and posterior cingulate gyrus and cuneus, the parahippocampal gyrus and the hippocampus. The schizophrenic patients did not show reduced activation compared to the healthy controls. They did, however, show failure of de-activation in the medial frontal cortex. Our negative finding with respect to hypoactivation during performance of a task requiring inhibition of prepotent responses suggests that brain functional abnormality in schizophrenia may not affect all aspects of executive function/cognitive control. The finding of medial frontal cortex failure of de-activation adds to existing findings of default mode network dysfunction in the disorder.

A Systematic Review of Magnetic Resonance Imaging Studies in Perinatally HIV-Infected Individuals.

Over the past few years, neuroimaging studies have been performed in young adults with perinatally acquired HIV (PHIV) to study the impact of HIV infection on the central nervous system (CNS), but no recent review have been published. This review aims to identify brain areas where PHIV eems to have greater impact taking into account demographic, behavioral, and clinical characteristics in PHIV infected patients. For this purpose, PubMed and Medline searches were carried out which included studies from 2010 to April 2020. We performed a systematic review and included 26 articles using structural (brain morphometry and diffusion tensor imaging) and functional magnetic resonance imaging methods involving 1182 PHIV-infected participants. Ample evidence has been provided of HIV effects on underlying brain structure. However, information recorded in the studies is commonly incomplete and results sometimes contradictory. In addition to future improvements and dissemination of tools for the developing brain MRI processing and analysis, the inclusion of data related to HIV infection itself (including clinical and immunovirological characteristics as well as detailed information about antiretroviral treatment such as age at ART initiation) may be of vital importance to the better understanding of the impact of the disease on CNS.

MAST1 variant causes mega-corpus-callosum syndrome with cortical malformations but without cerebellar hypoplasia.

We report the case of a Caucasian Spanish origin female who showed severe psychomotor developmental delay, hypotonia, strabismus, epilepsy, short stature, and poor verbal language development. Brain magnetic resonance imaging scans showed thickened corpus callosum, cortical malformations, and dilated and abnormal configuration of the lateral ventricles without hydrocephalus. Whole-exome sequence uncovered a de novo variant in the microtubule associated serine/threonine kinase 1 gene (MAST1; NM_014975.3:c.1565G>A:p.(Gly522Glu)) that encodes for the MAST1. Only 12 patients have been identified worldwide with 10 different variants in this gene: six patients with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations; two patients with microcephaly and cerebellar hypoplasia; two patients with autism, one patient with diplegia, and one patient with microcephaly and dysmorphism. Our patient shows a new phenotypic subtype defined by mega-corpus-callosum syndrome with cortical malformations without cerebellar hypoplasia. In conclusion, our data expand the phenotypic spectrum associated to MAST1 gene variants.

A novel de novo MTOR gain-of-function variant in a patient with Smith-Kingsmore syndrome and Antiphospholipid syndrome.

We report the clinical, biochemical and genetic findings from a Spanish girl of Caucasian origin who presented with macrocephaly, dysmorphic facial features, developmental delay, hypotonia, combined oxidative phosphorylation (OxPhos) deficiency, epilepsy and anti-phospholipid antibodies (aPL). Whole-exome sequencing (WES) uncovered a heterozygous variant in the MTOR gene (NM_004958.3: c.7235A>T: p.(Asp2412Val)) that encodes for the Serine/threonine-protein kinase mTOR. The substrates phosphorylation experiments demonstrated that this variant exerts its effect by gain-of-function (GOF) and autosomal dominant mechanism. GOF variants in this protein have been associated with Smith-Kingsmore syndrome (SKS), a rare autosomal dominant disorder characterized by intellectual disability, macrocephaly, seizure, developmental delay and dysmorphic facial features. Furthermore, the mTOR pathway has been demonstrated previously to be involved in many types of endothelium injuries including the antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by the production of aPL with recurrent vascular thrombosis. Therefore, our patient is the first one with an mTOR variant and diagnosed with SKS and APS. In conclusion, our data expand both the genetic and phenotypic spectrum associated with MTOR gene variants.

Hydrocephalus in pyridoxine-dependent epilepsy: New case and literature review.

INTRODUCTION: Pyridoxine-dependent epilepsy (PDE) is a rare disorder of the lysine metabolism, characterized by a pharmacoresistant epileptic encephalopathy that usually begins in the neonatal period. However, its phenotypic spectrum is wide and not limited to seizures. We report a new case of PDE who developed hydrocephalus, along with an exhaustive review of the literature. CASE REPORT: Our patient presented with seizures at 13 h of life. Antiepileptic drugs, vitamins and cofactors were required to achieve seizure control. Laboratory tests were congruent with PDE. She remained seizure-free until age five months, when seizures reappeared in the context of increasing head size and irritability. A cranial ultrasound showed hydrocephalus, for which she underwent ventriculoperitoneal shunting. DISCUSSION: Seven other patients with same features have been previously reported. Seizure onset occurred within the first 7 days in all patients. Most of the children developed hydrocephalus at 6-7 months of age. In 4 out of 7 a genetic mutation was identified, despite the accurate etiology of hydrocephalus was unknown in most of them. The case we report behaved similarly to the others previously described. We postulate that the pathogenesis of this complication could be related to the high expression of antiquitin in choroid plexus epithelium, where the cerebrospinal fluid is produced. CONCLUSIONS: patients with PDE should be closely monitored, since they may present severe complications. We highlight the development of hydrocephalus, an uncommon but potentially life-threatening problem reported in 8 patients up to present time.

Aneurisma micótico intracraneal en lactante con meningitis neumocócica / Intracranial mycotic aneurysm in a 5 month-old infant with pneumococcal meningitis

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Alteraciones del lenguaje en la cerebelitis aguda: más allá de la disartria / Language disorders in acute cerebellitis: beyond dysarthria

Introducción. La cerebelitis aguda es una de las principales causas de síndrome cerebeloso en la infancia. Entre un amplio elenco de manifestaciones, en el que predominan la cefalea y la ataxia, podemos encontrar otras menos habituales, aunque interesantes, como las alteraciones del lenguaje, más allá de la bien conocida disartria cerebelosa. Las diferentes combinaciones en que pueden aparecer los síntomas, especialmente cuando no se acompañan de ataxia, hacen de este cuadro un verdadero reto para el clínico. Casos clínicos. Se presentan dos pacientes, de 2 y 4 años, con clínica, pruebas de laboratorio y neuroimagen compatibles con cerebelitis aguda parainfecciosa, que asociaron una llamativa alteración del lenguaje, uno en forma de mutismo cerebeloso y otro en forma de hipofluencia y agramatismo, y este último cursaba además en ausencia de ataxia. La evolución de ambos casos fue buena, y persistieron leves alteraciones del habla en el seguimiento posterior. Conclusiones. Casos como éstos amplían el espectro de manifestaciones clínicas de la cerebelitis aguda. Cada vez cobra mayor importancia la participación del cerebelo en procesos neurocognitivos como el lenguaje y, aunque muchos aspectos son aún especulativos, alcanzar a definir su verdadero papel tendrá una repercusión en el diagnóstico, el tratamiento y el pronóstico a largo plazo de estos pacientes (AU)

Introduction. Acute cerebellitis is one of the main causes of cerebellar syndrome in infancy. Among the wide range of manifestations, headache and ataxia being the most predominant, we can find other less frequent, although nonetheless interesting, ones, such as language disorders, which go beyond the well-known cerebellar dysarthria. The different combinations in which the symptoms can appear, especially when not accompanied by ataxia, make the condition a real challenge for the clinician. Case reports. Two patients, aged 2 and 4 years, with clinical features, lab tests and neuroimaging results consistent with parainfectious acute cerebellitis. Both of them also presented a striking language disorder, one in the form of cerebellar mutism and the other in the form of hypofluency and agrammatism, the latter also developing in the absence of ataxia. Both cases progressed favourably, and mild speech alterations persisted in the follow-up visits. Conclusions. Cases such as these expand the range of clinical manifestations of acute cerebellitis. The involvement of the cerebellum in neurocognitive processes like language is becoming increasingly more important and, although many aspects are still only speculations, managing to define its true role will have important repercussions on the diagnosis, treatment and long-term prognosis of these patients (AU)

Posterior reversible encephalopathy syndrome (PRES): a rare condition after resection of posterior fossa tumors: two new cases and review of the literature.

INTRODUCTION: In 1996, Hinchey and colleagues coined the term "Posterior reversible encephalopathy syndrome" (PRES) to describe a condition seen in patients with acute neurological symptoms and reversible subcortical vasogenic edema predominantly involving parieto-occipital areas demonstrated in brain MRI. The occurrence of this phenomenon after surgical resection of CNS tumors is typically linked to pediatric cases. MATERIAL AND METHODS: Two new cases of PRES after posterior fossa surgery are reported. A thorough review of the literature is carried out with the purpose of updating and summarizing the main features regarding PRES in similar cases. Seven cases of PRES after resection of a posterior fossa tumor have been hitherto reported (4 patients were <20 years old). There is another pediatric case described after a ventriculoperitoneal shunting procedure in a patient with fourth ventricle ependymoma. Two resected tumors were ependymomas, 2 hemangiopericytomas in one patient, 1 pilocyticastrocytoma, 1 vestibular schwannoma, and 1 of the reported cases did not describe the final pathology diagnosis. CASE REPORTS: We present 2 new cases of PRES after surgical resection of a posterior fossa tumor (medulloblastoma in case 1 and ependymoma in case 2) in pediatric patients. Case 1 developed delayed seizures and altered mental status(10 days after surgical resection) after receiving treatment with bromocriptine for cerebellar mutism. Case 2 presented with generalized seizures and altered mental status within the first 48 postoperative hours followed by right hemiparesis. Both patients fully recovered and returned to neurological baseline status. A thorough review of the literature was carried out with the purpose of updating and summarizing the main features regarding PRES in similar cases. CONCLUSIONS: We report 2 new pediatric cases of posterior reversible encephalopathy syndrome (PRES) that developed after surgical resection of a posterior fossa tumor. Appropriate management includes supportive measures, antihypertensive agents, and antiepileptic drugs, if needed. Full recovery is the most likely outcome in line with previous articles.

Hipotensión intracraneal idiopática asociada a disrafismo espinal oculto / Idiopathic intracranial hypotension associated with occult spinal dysraphism

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Disección carotídea como causa de ictus perinatal / Carotid dissection as the cause of perinatal strokes

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Ictus en pacientes pediátricos con anemia falciforme / Stroke in paediatric patients with sickle-cell anaemia

Introducción. La anemia falciforme es la forma homocigota, grave, de drepanocitosis, un trastorno genético, frecuente en raza negra, caracterizado por la producción de hemoglobina S, anemia hemolítica crónica e isquemia tisular por alteración del flujo sanguíneo. Una cuarta parte de los pacientes presenta manifestaciones neurológicas; el 8-10% de los niños sufrirá un ictus. Objetivo. Analizar los casos de ictus en niños con anemia falciforme en nuestro centro. Pacientes y métodos. Estudio descriptivo retrospectivo de niños con anemia falciforme e ictus. Resultados. Se recogieron cinco pacientes (dos dominicanos y tres guineanos) con anemia falciforme e ictus; un paciente sufrió dos episodios ictales. La edad media fue de 27 meses. Cinco episodios fueron infartos isquémicos. El ictus fue la forma de inicio de la drepanocitosis en tres ocasiones. Dos de los ictus ocurrieron en un contexto de meningitis neumocócica. En cuatro pacientes hubo fiebre previa. La clínica inicial fue hemiparesia en cuatro casos. La hemoglobina media al diagnóstico de ictus fue de 6,5 g/dL. En tres pacientes se hallaron alteraciones en la ecografía transcraneal y, en todos los pacientes, lesiones en la resonancia magnética, que en la mitad eran bilaterales. Tras el ictus se inició un protocolo de régimen hipertransfusional, y sólo un paciente presentó un nuevo ictus, que desarrolló un síndrome moya-moya y fue sometido a una revascularización indirecta, con buena evolución, sin presentar nuevos eventos isquémicos posteriores. Conclusiones. La drepanocitosis es una enfermedad emergente en nuestro medio debido a la inmigración. Debe sospecharse en ictus pediátricos asociados a anemia, sobre todo en menores de 5 años de raza negra no sometidos a cribado neonatal (AU)

Introduction. Sickle-cell anaemia is the severe homozygotic form of drepanocytosis, a genetic disorder that often occurs among black people and which is characterised by the production of haemoglobin S, chronic hemolytic anaemia and tissue ischaemia due to alterations in blood flow. A quarter of the patients presented neurological manifestations; 8-10% of children will have a stroke. Aim. To analyse the cases of stroke in children with sickle-cell anaemia in our centre. Patients and methods. We conducted a retrospective descriptive study of children with sickle-cell anaemia and stroke. Results. Five patients (two Dominicans and three Guineans) with sickle-cell anaemia and stroke; one patient suffered two episodes of stroke. The mean age was 27 months. Five of the episodes were ischaemic infarctions. Stroke was the initial form of presentation of drepanocytosis on three occasions. Two of the strokes occurred within a context of pneumococcal meningitis. Four of the patients had previously reported fever. The initial clinical picture was hemiparesis in four cases. Mean haemoglobin on diagnosing the stroke was 6.5 g/dL. Transcranial ultrasound imaging revealed alterations in three patients and, in all the patients, magnetic resonance imaging revealed lesions, which were bilateral in half the cases. Following the stroke, a hypertransfusion regimen protocol was established and only one patient presented a new stroke. This same patient went on to develop moya-moya disease and was submitted to an indirect revascularisation; the patient progressed well, without presenting any new ischaemic events. Conclusions. Drepanocytosis is a disease that is emerging in our setting as a result of immigration. It should be suspected in cases of paediatric strokes associated to anaemia, above all in black children under the age of five who were not submitted to neonatal screening (AU)

[Stroke in paediatric patients with sickle-cell anaemia]. / Ictus en pacientes pediátricos con anemia falciforme.

INTRODUCTION: Sickle-cell anaemia is the severe homozygotic form of drepanocytosis, a genetic disorder that often occurs among black people and which is characterised by the production of haemoglobin S, chronic hemolytic anaemia and tissue ischaemia due to alterations in blood flow. A quarter of the patients presented neurological manifestations; 8-10% of children will have a stroke. AIM. To analyse the cases of stroke in children with sickle-cell anaemia in our centre. PATIENTS AND METHODS: We conducted a retrospective descriptive study of children with sickle-cell anaemia and stroke. RESULTS: Five patients (two Dominicans and three Guineans) with sickle-cell anaemia and stroke; one patient suffered two episodes of stroke. The mean age was 27 months. Five of the episodes were ischaemic infarctions. Stroke was the initial form of presentation of drepanocytosis on three occasions. Two of the strokes occurred within a context of pneumococcal meningitis. Four of the patients had previously reported fever. The initial clinical picture was hemiparesis in four cases. Mean haemoglobin on diagnosing the stroke was 6.5 g/dL. Transcranial ultrasound imaging revealed alterations in three patients and, in all the patients, magnetic resonance imaging revealed lesions, which were bilateral in half the cases. Following the stroke, a hypertransfusion regimen protocol was established and only one patient presented a new stroke. This same patient went on to develop moya-moya disease and was submitted to an indirect revascularisation; the patient progressed well, without presenting any new ischaemic events. CONCLUSIONS: Drepanocytosis is a disease that is emerging in our setting as a result of immigration. It should be suspected in cases of paediatric strokes associated to anaemia, above all in black children under the age of five who were not submitted to neonatal screening.

TITLE: Ictus en pacientes pediatricos con anemia falciforme.Introduccion. La anemia falciforme es la forma homocigota, grave, de drepanocitosis, un trastorno genetico, frecuente en raza negra, caracterizado por la produccion de hemoglobina S, anemia hemolitica cronica e isquemia tisular por alteracion del flujo sanguineo. Una cuarta parte de los pacientes presenta manifestaciones neurologicas; el 8-10% de los niños sufrira un ictus. Objetivo. Analizar los casos de ictus en niños con anemia falciforme en nuestro centro. Pacientes y metodos. Estudio descriptivo retrospectivo de niños con anemia falciforme e ictus. Resultados. Se recogieron cinco pacientes (dos dominicanos y tres guineanos) con anemia falciforme e ictus; un paciente sufrio dos episodios ictales. La edad media fue de 27 meses. Cinco episodios fueron infartos isquemicos. El ictus fue la forma de inicio de la drepanocitosis en tres ocasiones. Dos de los ictus ocurrieron en un contexto de meningitis neumococica. En cuatro pacientes hubo fiebre previa. La clinica inicial fue hemiparesia en cuatro casos. La hemoglobina media al diagnostico de ictus fue de 6,5 g/dL. En tres pacientes se hallaron alteraciones en la ecografia transcraneal y, en todos los pacientes, lesiones en la resonancia magnetica, que en la mitad eran bilaterales. Tras el ictus se inicio un protocolo de regimen hipertransfusional, y solo un paciente presento un nuevo ictus, que desarrollo un sindrome moya-moya y fue sometido a una revascularizacion indirecta, con buena evolucion, sin presentar nuevos eventos isquemicos posteriores. Conclusiones. La drepanocitosis es una enfermedad emergente en nuestro medio debido a la inmigracion. Debe sospecharse en ictus pediatricos asociados a anemia, sobre todo en menores de 5 años de raza negra no sometidos a cribado neonatal.